Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes

Abstract

This study aims to provide a detailed analysis of allogeneic stem cell transplantation (allo-SCT) outcomes in a large T-cell acute lymphoblastic leukemia (T-ALL) cohort with a specific emphasis on the effects of pre-transplant minimal residual disease (MRD) and disease subtype, including the aggressive early-thymic precursor (ETP) subtype. Data from 102 allo-SCT patients with a diagnosis of T-ALL from three centers were retrospectively analyzed. Patients were grouped into four T-ALL subtypes: ETP, early, cortical and mature. At 3 years, overall survival (OS), PFS, non-relapse mortality and cumulative incidence (CI) progression were 35, 33, 11 and 55%, respectively. Patients transplanted in first complete remission (CR1) had a 3-year OS of 62% versus those transplanted in CR2 or greater (24%) (hazards ratio 1.6, P=0.2). Patients with MRD positivity at the time of transplant had significantly higher rates of progression compared with those with MRD negativity (76 vs 34%, hazards ratio 2.8, P=0.006). There was no difference in OS, PFS or cumulative incidence (CI) progression between disease subtypes, including ETP (n=16). ETP patients transplanted in CR1 (n=10) had OS of 47%, comparable to other disease subtypes, suggesting that allo-SCT can overcome the poor prognosis associated with ETP. MRD status at transplant was highly predictive of disease relapse, suggesting novel therapies are necessary to improve transplant outcomes.

Allogeneic Hematopoietic Cell Transplantation for Adult T Cell Acute Lymphoblastic Leukemia

“…In our large contemporary cohort of T-ALL patients undergoing allogeneic HCT, including recipients of an RIC regimen and alternative donor HCT, one-third of the patients with high-risk disease survived for more than 5 years; however, relapse was the major cause of treatment failure. These data also identify disease status at transplantation as the most important risk factor for survival, confirming previous studies demonstrating the prognostic significance of achieving CR at the time of transplantation [4–6]. A single-institution study evaluated 53 patients with high risk T-ALL who underwent allogeneic HCT [4].…”

“…A recent study reported by Brammer et al [6] found that the presence of minimal residual disease (MRD) at the time of HCT is highly predictive of relapse. Although we did not have information on MRD status at HCT, future studies will need to consider its impact on transplantation outcomes.…”

“…Allogeneic hematopoietic cell transplantation (HCT) is typically recommended for adults with T-ALL in second or later complete remission (CR2+), but also may be offered to patients in first CR (CR1) with high-risk features. There have been few reports on allogeneic HCT for the treatment of T-ALL [4–6]. In a prospective cohort of 356 adults with T-ALL treated uniformly between 1993 and 2006 on the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group 2993, a donor/no-donor comparison demonstrated superior 5-year survival in patients with matched sibling donors compared with those without donors (61% versus 46%; P = .02), as a result of less relapse (25% versus 51% at 5 years; P < .001) [1].…”

Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease

“…The presence of MRD is usually associated with an increased risk of disease recurrence and worse outcome [22]. Relative to MRD-negative patients, MRD-positive patients in CR1 undergoing allo-HSCT had a significantly worse outcome with a 3-year cumulative incidence of relapse that approximated 60% to 76%, resulting in an estimated survival of approximately 20% to 30%, with MRD being the dominant risk factor for adverse outcomes [8,23,24]. Because these outcomes with current approaches to allo-HSCT for MRD-positive CR patients are unsatisfactory, it is appealing to consider treatment intensifications during induction/postremission therapy and/or before transplantation in an attempt to induce an MRD negative state [25].…”

Advances in adult acute lymphoblastic leukemia therapy

“…Therefore, every effort should be made to cure T cell ALL with active frontline therapies, and early referral for alloHCT should be emphasized for high-risk features based on genetics, MRD response and possibly phenotype (early thymic T cell). In a retrospective analysis, alloHCT produced a 3-year OS of 62% for adults with T cell ALL in first CR, and no difference in outcomes was noted on the basis of leukemia phenotype (early thymic vs. others) [143].…”